Augmenting Mindfulness Training Through Experience-driven Neurofeedback Devices (ATTEND). Meditation is the second most frequently used mind-body therapy in the US, with demonstrated clinical benefits for stress, anxiety, depression, and addiction. However, no neurobiological markers of meditative states have been clearly delineated. The lack of objective tools for assessing mindfulness is a fundamental obstacle to further scientific progress. The posterior cingulate cortex (PCC) has recently been identified as a promising neuroimaging-based marker of meditation, as this brain region is activated during stress and mind-wandering, but deactivated during mindfulness (Brewer 2011). At the same time, methodological advances in real-time fMRI neurofeedback (RTFB) allow delivery of feedback from the PCC to augment meditation acquisition that is traditionally delivered through Mindfulness-Based Stress Reduction (MBSR) programs. In the proposed study, Aim 1 will confirm that PCC deactivation corresponds to the subjective experience of meditation. To achieve this, PCC activity will be measured in 24 experienced meditators in a 4-step series of fMRI tasks progressing from: (1) meditation, (2) meditation with simulated RTFB, (3) meditation with RTFB from the PCC, to (4) volitional deactivation of PCC activity. We anticipate that meditators will report a high correspondence between decreased PCC activity and subjective meditation in Step 3 and will be able to volitionally deactivate their PCC by meditation in Step 4. These data will confirm the PCC as a sensitive neuroimaging marker of the meditative state. Aim 2 will demonstrate that RTFB from the PCC augments MBSR as assessed by PCC deactivation during meditation. To achieve this, 129 novice meditators will be randomized to three groups. Group 1: MBSR with RTFB training from the PCC, Group 2: MBSR with RTFB training from a control region, or Group 3: MBSR alone. We anticipate that Group 1 will show significantly greater pre- to post-MBSR percent signal change in the PCC during meditation. These results will demonstrate that RTFB can augment MBSR training. Aim 3 will show that MBSR with RTFB from the PCC leads to reduced stress and improved attention. Stress will be measured using the perceived stress scale (PSS), and attention will be measured using the Rapid Visual Information Processing task (RVIP), pre- and post-MBSR, and at a 3-month follow-up. We anticipate that percent signal change in the PCC during meditation from Aim 2 will predict change in PSS and RVIP scores pre- to post-MBSR and pre- to 3 months post-MBSR. These results will demonstrate that RTFB augmentation of MBSR improves cognition and health-related outcomes such as stress. This project has numerous benefits for society, as it will be the first to confirm neural targets of meditation, and to translate this knowledge into strategies to improve health through augmentation of MBSR.